This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. EGFR and its related cell apoptosis and cell survival pathways play an important role in the progress of pathogenesis of skin cancer upon chronic UV radiation. We previously reported that UV radiation induces EGFR activation. Our preliminary studies suggest that activation of p38 pathway is responsible for UV-induced cell apoptosis, whereas activation of Akt pathway protects cells from death. Further, UV radiation induces activation of mTOR that is critical for cell survival. Although the molecular mechanisms of UV-induced skin cancers are still not well understood, a number of approaches are sought to protect against UV radiation. The most attractive one is the potentially clinical usage of oligodeoxynucleotides containing CpG motif (or CpG-ODNs), which are well equipped to activate immune cells and function as adjuvants for vaccine strategy against allergy and cancer. Our previous studies have demonstrated that CpG-ODN activates Akt. Our preliminary data suggests that mTOR complex 1 (TORC1) is a downstream target of CpG-ODN/Akt axis. Further, we show that CpG-ODN protects against UV-induced cell death. Nevertheless, the molecular mechanisms underlying the activation of cell apoptosis and survival by UV and the protective effect of CpG-ODN are still largely unknown. Thus, we have formulated three specific aims to elucidate these issues: How does p38 trigger apoptosis in response to UV radiation? How does UV induce Akt and mTORC1 activation? How does CpG-ODN protect against UV-induced cell death? Our study will delineate novel cell signaling pathways through which UV induces apoptosis and CpG-ODN protects against UV-induced cell death.